Polymer Chemistry Laboratory, Department of Applied Chemistry, Indian Institute of Technology (ISM) (Indian School of Mines), Dhanbad 826004, India.
Biomaterials and Tissue Engineering Laboratory, School of Medical Science & Technology, Indian Institute of Technology, Kharagpur 721302, India.
Carbohydr Polym. 2017 Sep 1;171:27-38. doi: 10.1016/j.carbpol.2017.04.068. Epub 2017 Apr 27.
The present article demonstrates the targeted delivery of doxorubicin hydrochloride to human osteosarcoma cancer cell lines (MG 63) using functionalized dextrin based crosslinked, pH responsive and biocompatible nanogel. The nanogel has been prepared through Michael-type addition reaction using dextrin (Dxt), N, N'-methylene bisacrylamide (MBA, as crosslinker), acrylic acid (AA, as monomer) and potassium persulfate (KPS, as initiator). The structure, composition, morphology of the nanogel have been explored using FTIR and H NMR spectroscopy, XRD, TGA, DSC, CHN and AFM analyses. The TEM analysis confirmed that the size of nanogel appeared within 100nm, while DLS study indicates that the diameter of the nanogel remained between 113 and 126nm. The AFM study implied the porous morphology of the synthesized nanogel. The rheological study suggests the gel behaviour of the synthesized nanogel at 37±0.1°C. Difference in% swelling at pH 5.5 and 7.4 indicates pH-responsiveness of the nanogel. The in vitro cytocompatibility results ascertained that the nanogel is non-toxic to human mesenchymal stem cells (hMSCs). In vitro cellular uptake study confirmed that FITC-loaded nanogel can cross the cellular membrane and be well uptake by the cell cytoplasm. The nanogel could efficiently encapsulate doxorubicin hydrochloride (Dox) with the loading efficiency of 27±0.2% after 72h. The Dox-loaded nanogel demonstrates anti-cancer activity towards MG 63 cancer cells and release the encapsulated drug in a controlled way.
本文展示了使用基于功能化糊精的交联、pH 响应和生物相容的纳米凝胶将盐酸多柔比星靶向递送至人骨肉瘤癌细胞系(MG63)。纳米凝胶是通过迈克尔型加成反应制备的,使用糊精(Dxt)、N,N'-亚甲基双丙烯酰胺(MBA,作为交联剂)、丙烯酸(AA,作为单体)和过硫酸钾(KPS,作为引发剂)。使用 FTIR 和 H NMR 光谱、XRD、TGA、DSC、CHN 和 AFM 分析研究了纳米凝胶的结构、组成和形态。TEM 分析证实纳米凝胶的尺寸在 100nm 以内,而 DLS 研究表明纳米凝胶的直径在 113nm 至 126nm 之间。AFM 研究表明合成的纳米凝胶具有多孔形态。流变学研究表明,在 37±0.1°C 时,合成的纳米凝胶具有凝胶行为。在 pH 5.5 和 7.4 下的溶胀率差异表明纳米凝胶具有 pH 响应性。体外细胞相容性结果证实纳米凝胶对人骨髓间充质干细胞(hMSCs)无毒性。体外细胞摄取研究证实,FITC 负载的纳米凝胶可以穿过细胞膜并被细胞质很好地摄取。纳米凝胶可以在 72 小时后以 27±0.2%的载药效率有效地包载盐酸多柔比星(Dox)。载药的纳米凝胶对 MG63 癌细胞具有抗癌活性,并以可控的方式释放封装的药物。